title: Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA.
abstract: Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C.
authors.affiliation: Dermatology Department, University of Newcastle upon Tyne, England.
authors.forename: P S
authors.initials: PS
authors.lastname: Friedmann
authors.forename: F E
authors.initials: FE
authors.lastname: Wren
authors.forename: J N
authors.initials: JN
authors.lastname: Matthews
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008546:Melanoma, Experimental; D051379:Mice; D015230:Prostaglandin D2 / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D004075:Diglycerides; D005989:Glycerides; D008543:Melanins; C038237:1-oleoyl-2-acetylglycerol; D015237:Dinoprost; D000527:Alprostadil; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2